Sediment Transport Model Including Short-Lived Radioisotopes: Model Description and Idealized Test Cases

Geochronologies derived from sediment cores in coastal locations are often used to infer event bed characteristics such as deposit thicknesses and accumulation rates. Such studies commonly use naturally occurring, short-lived radioisotopes, such as Beryllium-7 (Be-7) and Thorium-234 (Th-234), to study depositional and post-depositional processes. These radioisotope activities, however, are not generally represented in sediment transport models that characterize coastal flood and storm deposition with grain size patterns and deposit thicknesses. We modified the Community Sediment Transport Modeling System (CSTMS) to account for reactive tracers and used this capability to represent the behavior of these short-lived radioisotopes on the sediment bed. This paper describes the model and presents results from a set of idealized, one-dimensional (vertical) test cases. The model configuration represented fluvial deposition followed by periods of episodic storm resuspension. Sensitivity tests explored the influence on seabed radioisotope profiles by the intensities of bioturbation and wave resuspension and the thickness of fluvial deposits. The intensity of biodiffusion affected the persistence of fluvial event beds as evidenced by Be-7. Both resuspension and biodiffusion increased the modeled seabed inventory of Th-234. A thick fluvial deposit increased the seabed inventory of Be-7 and Th-234 but mixing over time greatly reduced the difference in inventory of Th-234 in fluvial deposits of different thicknesses

Predictive blood biomarkers and brain changes associated with age-related cognitive decline

Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and glial fibrillary acidic protein as promising biomarkers for Alzheimer's disease. While these blood biomarkers are promising for distinguishing people with Alzheimer's disease from healthy controls, their predictive validity for age-related cognitive decline without dementia remains unclear. Further, while tau phosphorylated at threonine 181 is a promising biomarker, the distribution of this phospho-epitope of tau in the brain is unknown. Here, we tested whether plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and fibrillary acidic protein predict cognitive decline between ages 72 and 82 in 195 participants in the Lothian birth cohorts 1936 study of cognitive ageing. We further examined post-mortem brain samples from temporal cortex to determine the distribution of tau phosphorylated at threonine 181 in the brain. Several forms of tau phosphorylated at threonine 181 have been shown to contribute to synapse degeneration in Alzheimer's disease, which correlates closely with cognitive decline in this form of dementia, but to date, there have not been investigations of whether tau phosphorylated at threonine 181 is found in synapses in Alzheimer's disease or healthy ageing brain. It was also previously unclear whether tau phosphorylated at threonine 181 accumulated in dystrophic neurites around plaques, which could contribute to tau leakage to the periphery due to impaired membrane integrity in dystrophies. Brain homogenate and biochemically enriched synaptic fractions were examined with western blot to examine tau phosphorylated at threonine 181 levels between groups (n = 10-12 per group), and synaptic and astrocytic localization of tau phosphorylated at threonine 181 were examined using array tomography (n = 6-15 per group), and localization of tau phosphorylated at threonine 181 in plaque-associated dystrophic neurites with associated gliosis were examined with standard immunofluorescence (n = 8-9 per group). Elevated baseline plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein predicted steeper general cognitive decline during ageing. Further, increasing tau phosphorylated at threonine 181 over time predicted general cognitive decline in females only. Change in plasma tau phosphorylated at threonine 181 remained a significant predictor of g factor decline when taking into account Alzheimer's disease polygenic risk score, indicating that the increase of blood tau phosphorylated at threonine 181 in this cohort was not only due to incipient Alzheimer's disease. Tau phosphorylated at threonine 181 was observed in synapses and astrocytes in both healthy ageing and Alzheimer's disease brain. We observed that a significantly higher proportion of synapses contain tau phosphorylated at threonine 181 in Alzheimer's disease relative to aged controls. Aged controls with pre-morbid lifetime cognitive resilience had significantly more tau phosphorylated at threonine 181 in fibrillary acidic protein-positive astrocytes than those with pre-morbid lifetime cognitive decline. Further, tau phosphorylated at threonine 181 was found in dystrophic neurites around plaques and in some neurofibrillary tangles. The presence of tau phosphorylated at threonine 181 in plaque-associated dystrophies may be a source of leakage of tau out of neurons that eventually enters the blood. Together, these data indicate that plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein may be useful biomarkers of age-related cognitive decline, and that efficient clearance of tau phosphorylated at threonine 181 by astrocytes may promote cognitive resilience

Predictive blood biomarkers and brain changes associated with age-related cognitive decline

Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and glial fibrillary acidic protein as promising biomarkers for Alzheimer's disease. While these blood biomarkers are promising for distinguishing people with Alzheimer's disease from healthy controls, their predictive validity for age-related cognitive decline without dementia remains unclear. Further, while tau phosphorylated at threonine 181 is a promising biomarker, the distribution of this phospho-epitope of tau in the brain is unknown. Here, we tested whether plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and fibrillary acidic protein predict cognitive decline between ages 72 and 82 in 195 participants in the Lothian birth cohorts 1936 study of cognitive ageing. We further examined post-mortem brain samples from temporal cortex to determine the distribution of tau phosphorylated at threonine 181 in the brain. Several forms of tau phosphorylated at threonine 181 have been shown to contribute to synapse degeneration in Alzheimer's disease, which correlates closely with cognitive decline in this form of dementia, but to date, there have not been investigations of whether tau phosphorylated at threonine 181 is found in synapses in Alzheimer's disease or healthy ageing brain. It was also previously unclear whether tau phosphorylated at threonine 181 accumulated in dystrophic neurites around plaques, which could contribute to tau leakage to the periphery due to impaired membrane integrity in dystrophies. Brain homogenate and biochemically enriched synaptic fractions were examined with western blot to examine tau phosphorylated at threonine 181 levels between groups (n = 10-12 per group), and synaptic and astrocytic localization of tau phosphorylated at threonine 181 were examined using array tomography (n = 6-15 per group), and localization of tau phosphorylated at threonine 181 in plaque-associated dystrophic neurites with associated gliosis were examined with standard immunofluorescence (n = 8-9 per group). Elevated baseline plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein predicted steeper general cognitive decline during ageing. Further, increasing tau phosphorylated at threonine 181 over time predicted general cognitive decline in females only. Change in plasma tau phosphorylated at threonine 181 remained a significant predictor of g factor decline when taking into account Alzheimer's disease polygenic risk score, indicating that the increase of blood tau phosphorylated at threonine 181 in this cohort was not only due to incipient Alzheimer's disease. Tau phosphorylated at threonine 181 was observed in synapses and astrocytes in both healthy ageing and Alzheimer's disease brain. We observed that a significantly higher proportion of synapses contain tau phosphorylated at threonine 181 in Alzheimer's disease relative to aged controls. Aged controls with pre-morbid lifetime cognitive resilience had significantly more tau phosphorylated at threonine 181 in fibrillary acidic protein-positive astrocytes than those with pre-morbid lifetime cognitive decline. Further, tau phosphorylated at threonine 181 was found in dystrophic neurites around plaques and in some neurofibrillary tangles. The presence of tau phosphorylated at threonine 181 in plaque-associated dystrophies may be a source of leakage of tau out of neurons that eventually enters the blood. Together, these data indicate that plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein may be useful biomarkers of age-related cognitive decline, and that efficient clearance of tau phosphorylated at threonine 181 by astrocytes may promote cognitive resilience

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Generation of twenty four induced pluripotent stem cell lines from twenty four members of the Lothian 4 Birth Cohort 1936

Cognitive decline is among the most feared aspects of ageing. We have generated induced pluripotent stem cells (iPSCs) from 24 people from the Lothian Birth Cohort 1936, whose cognitive ability was tested in childhood and in older age. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating oriP/EBNA1 backbone plasmids expressing six iPSC reprogramming factors (OCT3/4 (POU5F1), SOX2, KLF4, L-Myc, shp53, Lin28, SV40LT). All lines demonstrated STR matched karyotype and pluripotency was validated by multiple methods. These iPSC lines are a valuable resource to study molecular mechanisms underlying individual differences in cognitive ageing and resilience to age-related neurodegenerative diseases

The Seventh Data Release of the Sloan Digital Sky Survey

This paper describes the Seventh Data Release of the Sloan Digital Sky Survey (SDSS), marking the completion of the original goals of the SDSS and the end of the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most of the roughly 2000 deg^2 increment over the previous data release lying in regions of low Galactic latitude. The catalog contains five-band photometry for 357 million distinct objects. The survey also includes repeat photometry over 250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A coaddition of these data goes roughly two magnitudes fainter than the main survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2 in the Northern Galactic Cap, closing the gap that was present in previous data releases. There are over 1.6 million spectra in total, including 930,000 galaxies, 120,000 quasars, and 460,000 stars. The data release includes improved stellar photometry at low Galactic latitude. The astrometry has all been recalibrated with the second version of the USNO CCD Astrograph Catalog (UCAC-2), reducing the rms statistical errors at the bright end to 45 milli-arcseconds per coordinate. A systematic error in bright galaxy photometr is less severe than previously reported for the majority of galaxies. Finally, we describe a series of improvements to the spectroscopic reductions, including better flat-fielding and improved wavelength calibration at the blue end, better processing of objects with extremely strong narrow emission lines, and an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor correction

The Australia Telescope 20GHz Survey: Hardware, Observing Strategy, and Scanning Survey Catalog

The Australia Telescope 20GHz (AT20G) survey is a large area (2{\pi} sr), sensitive (40mJy), high frequency (20GHz) survey of the southern sky. The survey was conducted in two parts: an initial fast scanning survey, and a series of more accurate follow-up observations. The follow-up survey catalog has been presented by Murphy et al. 2010. In this paper we discuss the hardware setup and scanning survey strategy as well as the production of the scanning survey catalog.Comment: 32 pages, 20 figures, accepted for publication in experimental astronom

Models of peer support to remediate post-intensive care syndrome: A report developed by the SCCM Thrive International Peer Support Collaborative

Objective: Patients and caregivers can experience a range of physical, psychological, and cognitive problems following critical care discharge. The use of peer support has been proposed as an innovative support mechanism. Design: We sought to identify technical, safety and procedural aspects of existing operational models of peer support, among the Society of Critical Care Medicine Thrive Peer Support Collaborative. We also sought to categorize key distinctions between these models and elucidate barriers and facilitators to implementation. Subjects: 17 Thrive sites from the USA, UK, and Australia were represented by a range of healthcare professionals. Interventions: Via an iterative process of in-person and email/conference calls, members of the Collaborative, defined the key areas on which peer support models could be defined and compared; collected detailed self-reports from all sites; reviewed the information and identified clusters of models. Barriers and challenges to implementation of peer support models were also documented. Results: Within the Thrive Collaborative, six general models of peer support were identified: Community based, Psychologist-led outpatient, Models based within ICU follow-up clinics, Online, Groups based within ICU and Peer mentor models. The most common barriers to implementation were: recruitment to groups, personnel input and training: sustainability and funding, risk management and measuring success. Conclusion: A number of different models of peer support are currently being developed to help patients and families recover and grow in the post-critical care setting